A Deep Intronic Target For Splicing Correction On Spinal Muscular Atrophy Gene


Ontology type: sgo:Patent     


Patent Info

DATE

N/A

AUTHORS

SINGH, RAVINDRA N. , SINGH, NATALIA N.

ABSTRACT

ABSTRACT The present invention is directed to methods and compositions for blocking the effect of the intronic inhibitory splicing region of intron 7 of the SMN2 gene. The compositions and methods of the instant invention include short oligonucleotide reagents (e.g., oligoribonucleotides) that effectively target sites in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The target regions include a unique RNA structure and a 6-nucleotide long sequence that is essential for initiating a long distance steric inhibitory interaction. The identified region provides a novel target deep within SMN2 intron 7. Intronic targets are highly desirable as annealing of an ASO to an intron does not interfere with translation and transport of mRNA. The invention also provides opportunity to employ a short antisense oligonucleotide or a small compound against the unique RNA structure responsible of SMN2 exon 7 skipping in SMA. More... »

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ABSTRACT The present invention is directed to methods and compositions for blocking the effect of the intronic inhibitory splicing region of intron 7 of the SMN2 gene. The compositions and methods of the instant invention include short oligonucleotide reagents (e.g., oligoribonucleotides) that effectively target sites in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The target regions include a unique RNA structure and a 6-nucleotide long sequence that is essential for initiating a long distance steric inhibitory interaction. The identified region provides a novel target deep within SMN2 intron 7. Intronic targets are highly desirable as annealing of an ASO to an intron does not interfere with translation and transport of mRNA. The invention also provides opportunity to employ a short antisense oligonucleotide or a small compound against the unique RNA structure responsible of SMN2 exon 7 skipping in SMA.

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79 long sequence
80 method
81 novel target
82 oligoribonucleotides
83 short oligonucleotides
84 small compound
85 spinal muscular atrophy
86 splicing
87 target
88 target region
89 target site
90 transcript
91 translation
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